Project Summary Non-medical prescription opioid use (NMPOU) is a developing crisis, with prescription opioid related deaths exceeding those related to cocaine and heroin combined and estimated societal costs of over $55 billion in 2014. While agonist therapies, such as buprenorphine and methadone, have been indispensable in providing a path to recovery for these individuals, they primarily focus on reducing withdrawal symptoms. While it is true that withdrawal precipitates relapse, it is important to note that pain management is endorsed by a majority of non-medical prescription opioid users as a primary factor contributing to their continued use. Individuals with prescription opioid addiction often struggle with compliance, costs or dislike the necessity of continued medication. It is critical that the field explores non-pharmacological methods that are able to treat common causes of continued non-medical opioid use, specifically pain and craving. Repetitive transcranial magnetic stimulation (rTMS) is a form of non-invasive brain stimulation that can be targeted to specific cortical locations. The left dorsolateral prefrontal cortex (DLPFC) is a key executive control area and rTMS at this site is currently an FDA-approved treatment for depression. Furthermore, left DLPFC rTMS is currently under investigation as a treatment for pain and other substance use disorders. The primary goal of this F31 research proposal is to determine whether rTMS administered to treatment seeking NMPOU patients can affect the neural response to acute pain after a single session (Aim 1), if multiple sessions amplify these results (Aim 2) and if these effects are clinically meaningful on both on pain and craving (Exploratory Aim). This will be buttressed by a research training plan targeted at didactic and hands-on training in neuroimaging and brain stimulation (mentor: Hanlon), opioid dependence (mentor: Back) and pain processing (mentor: Borckardt). The feasibility of this project is enhanced through a partnership with MUSC?s Center for Drug and Alcohol Programs (CDAP) and its status as a sub-study as part of a larger protocol within in Dr. Hanlon?s laboratory. For this proposal, forty treatment seeking, prescription opioid dependent individuals will be recruited from CDAP and randomized to receive 10 days of real or sham rTMS in a double blind fashion. Immediately before and after the first (Aim 1) and last rTMS session (Aim 2) our participants will undergo thermal stimulation within the MRI environment to determine the neural response to painful stimuli. At multiple timepoints, thermal thresholds and craving will be evaluated. This proposal consists of three, interconnected training goals. First, the candidate will undergo training on the delivery of sham-controlled, double blind, left DLPFC rTMS, a tool that is gaining importance in substance abuse treatment. Secondly, the candidate will gain valuable experience in the recruitment and assessment of a population of non-medical prescription opioid users. Thirdly, in order to determine the neurobiological correlates of painful stimuli in this population, the candidate will be mentored on the delivery, collection and analysis of concurrent thermal stimulation and functional neuroimaging.